Functional promoter -94 ins/del ATTG polymorphism in NFKB1 gene is associated with bladder cancer risk in a Chinese population

PLoS One. 2013 Aug 20;8(8):e71604. doi: 10.1371/journal.pone.0071604. eCollection 2013.

Abstract

Background: A functional -94 insertion/deletion polymorphism (rs28362491) in the promoter of the NFKB1 gene was reported to influence NFKB1 expression and confer susceptibility to different types of cancer. This study aims to determine whether the polymorphism is associated with risk of bladder cancer.

Materials and methods: TaqMan assay was used to determine genotype among 609 cases and 640 controls in a Chinese population. Logistic regression was used to assess the association between the polymorphism and bladder cancer risk, and quantitative real-time polymerase chain reaction was used to determine NFKB1 mRNA expression.

Results: Compared with the ins/ins/ins/del genotypes, the del/del genotype was associated with a significantly increased risk of bladder cancer [adjusted odd ratio (OR) = 1.92, 95% confidence interval (CI) = 1.42-2.59]. The increased risk was more prominent among subjects over 65 years old (OR = 2.37, 95% CI= 1.52-3.70), male subjects (OR = 1.97, 95% CI = 1.40-2.79) and subjects with self-reported family history of cancer (OR = 3.59, 95% CI = 1.19-10.9). Furthermore, the polymorphism was associated with a higher risk of developing non-muscle invasive bladder cancer (OR= 2.07, 95% CI= 1.51-2.85), grade 1 bladder cancer (OR = 2.40, 95% CI = 1.68-3.43), single tumor bladder cancer (OR = 2.04, 95% CI = 1.48-2.82) and smaller tumor size bladder cancer (OR = 2.10, 95% CI= 1.51-2.92). The expression of NFKB1 mRNA in bladder cancer tissues with homozygous insertion genotype was higher than that with deletion allele.

Conclusions: In conclusion, the -94 ins/del ATTG polymorphism in NFKB1 promoter may contribute to the etiology of bladder cancer in the Chinese population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asian People / genetics*
  • Base Sequence
  • Case-Control Studies
  • China
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Frequency / genetics
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • INDEL Mutation / genetics*
  • Male
  • Middle Aged
  • NF-kappa B p50 Subunit / genetics*
  • NF-kappa B p50 Subunit / metabolism
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Risk Factors
  • Smoking / adverse effects
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology

Substances

  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • RNA, Messenger

Grants and funding

This work was supported by the Program for Development of Innovative Research Team of the First Affiliated Hospital of Nanjing Medical University, the Provincial Initiative Program for Excellency Disciplines of Jiangsu Province, the National Natural Science Foundation of China (grants No. 81272832 and 81201997), the Natural Science Foundation of Jiangsu Province (grant No. BK2011848) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.